A contributing factor to the development of arthritis is the inappropriate proteolytic destruction of the aggrecan component of cartilage by the proteolytic enzyme aggrecanase. The immune system signal molecule interleukin 2 (IL-2) activates aggrecanase; in fact, IL-2 blockers are sometimes used to treat arthritis. Studies were undertaken to determine whether inhibitors of aggrecanase could counteract the effects of IL-2. Pieces of cartilage were incubated in media with various additions and the amount of aggrecan destruction was measured as a function of time. Aggrecan degradation was measured by the release of glycosaminoglycan. What is the rationale for this assay? Aggrecan is a transferase enzyme that adds glycosaminoglycans to glycoproteins, and these glycosaminoglycans remain free if aggrecan is degraded. Aggrecan is a lectin that binds glycosaminoglycan ligands, and aggrecan releases these glycosaminoglycans as it is degraded. Aggrecan inhibits the removal of glycosaminoglycans from proteoglycans, and aggrecan degradation allows this removal to proceed. O Aggrecan is heavily decorated with glycosaminoglycans, and the release of these glycosaminoglycans is a sign of aggrecan degradation.
A contributing factor to the development of arthritis is the inappropriate proteolytic destruction of the aggrecan component of cartilage by the proteolytic enzyme aggrecanase. The immune system signal molecule interleukin 2 (IL-2) activates aggrecanase; in fact, IL-2 blockers are sometimes used to treat arthritis. Studies were undertaken to determine whether inhibitors of aggrecanase could counteract the effects of IL-2. Pieces of cartilage were incubated in media with various additions and the amount of aggrecan destruction was measured as a function of time. Aggrecan degradation was measured by the release of glycosaminoglycan. What is the rationale for this assay? Aggrecan is a transferase enzyme that adds glycosaminoglycans to glycoproteins, and these glycosaminoglycans remain free if aggrecan is degraded. Aggrecan is a lectin that binds glycosaminoglycan ligands, and aggrecan releases these glycosaminoglycans as it is degraded. Aggrecan inhibits the removal of glycosaminoglycans from proteoglycans, and aggrecan degradation allows this removal to proceed. O Aggrecan is heavily decorated with glycosaminoglycans, and the release of these glycosaminoglycans is a sign of aggrecan degradation.
Biochemistry
9th Edition
ISBN:9781319114671
Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Chapter1: Biochemistry: An Evolving Science
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